We have proposed a developmental concept of cancer suggesting that neoplasms are a pathology of the normal process of tissue renewal, and that enhancement of differentiation could serve as an alternative to cytotoxic therapy in treatment of tumors. Recent evidence indicates that one embryonic field can direct differentiation of a tumor along normal lines. We will test the ability of embryonic fields to influence differentiation in selected tumors of close correspondence and analyze the mechanism involved to see if there is a possibility for therapy. A series of experiments is proposed to determine if the endocrine cells of an adenocarcinoma of the colon are of endodermal origin. These experiments will involve cloning of the tumors and it will help solve the controversy surrounding the long-held dogma that these cells are probably of neural crest origin. The final proposal, in line with the developmental concept, is to examine the possible relationship of benign and malignant tumors. It is our belief that malignant tumors will develop from undifferentiated normal stem cells and that benign tumors will develop from differentiated cells still capable of one round of mitosis. We will separate stem cells on the one hand from differentiated elements on the other, transform them and test them to see if the resultant lines are benign or malignant.